Mutations in the coding region of the insulin promoter factor 1 gene are not a common cause of maturity-onset diabetes of the young in Japanese subjects.

iabetes is a group of metabolic disorders char-acterized by a hyperglycemia resulting fromdefects in insulin secretion, insulin action, orboth (1). A feature of all forms of diabetes is pan-creatic -cell dysfunction caused by either immune-medi-ated -cell destruction in type 1 diabetes or failure of the -cell to compensate to meet the increasing demand for insulinin type 2 diabetes and maturity-onset diabetes of the young(MODY). A better understanding of the molecular basis of -cell dysfunction in nonimmune-mediated forms of diabeteshas come from genetic studies of MODY, a monogenic formof diabetes characterized by autosomal-dominant inheri-tance, onset usually before age 25 years, and abnormal pat-tern of glucose-stimulated insulin secretion (2). Recent stud-ies have shown a central role for transcription factors in theetiology of this form of diabetes including the liver- e n r i c h e d ,but not liver-restricted, transcription factors hepatocytenuclear factor- 1 ( H N F - 1 ) (3), HNF-1 (4), and HNF-4(5), as well as insulin promoter factor 1 (IPF-1) (also knownas STF-1, IDX-1, and PDX-1) (6,7), which regulates early pan-creatic development and the expression of a number of - c e l lgenes including insulin, GLUT2, glucokinase, and amylin(8–11). HNF-1 , HNF-1 , and IPF-1 are members of thehomeodomain-containing transcription factor superfamily,and HNF-4 is a member of the nuclear receptor superfam-i l y . Mutations in the HNF-1 gene are a relatively commoncause of MODY, whereas mutations in the HNF-1 and HNF-4 genes are less common. Since the frequency of mutationsin the IPF-1 gene (